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1804 Real World Efficacy and Safety of Momelotinib for Myelofibrosis: Evaluation of a UK-Wide Study Confirms 40% Anaemia Response Rate in a Non-Clinical Trial Cohort

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Clinical Research, Real-world evidence, Adverse Events
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Alexandros Rampotas, MBBS, MRCP1*, Elena Torre2*, Luke Carter-Brzezinski, MBBChir3*, Andrea Duminuco2*, Llywelyn Cadman-Davies2*, Ashlyn Chee4*, Fotios Panitsas, MD5*, Samah Alimam, MD, PhD6*, Dragana Milojkovic, MBBS, MRCP, FRCPath, PhD7*, Richard Kaczmarski8*, Louise Fraser9*, Rebecca Frewin10*, Kate Foley11*, Catherine Hockings12*, Alesia Khan13*, Rhys Williams10*, Jennifer Ryan14*, Kawai Yip, MD15*, Kyaw Htin Thaw16*, Amna Sheikh16*, Frances Wadelin17*, Anna L Godfrey18*, Chun Huat Teh19*, Andrew J. Wilson20*, Jonathan Lambert, PhD, BSc, BMBS, FRCP, FRCPath21*, Adam J Mead, PhD, MRCP, FRCPath22, Donal P McLornan, MD, PhD23*, Andrew J Innes, MD, PhD24*, Andrew McGregor25*, Tim Somervaille, PhD FRCP FRCPath26, Claire Harrison27, Patrick Harrington16* and Bethan Psaila, MD, PhD28,29

1UCL Cancer Institute, University College London, London, United Kingdom
2Haematology Department, Guy's and St Thomas' Hospital NHS Foundation Trust, London, United Kingdom
3Haematology Department, The Christie NHS Foundation Trust, Manchester, United Kingdom
4Haematology Department, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
5Haematology Department, Laikon General Hospital of Athens, Athens, Greece
6University College of London Hospitals NHS Foundation Trust, London, United Kingdom
7Hammersmith Hospital, Imperial College Healthcare NHS Trust, London, GBR
8Haematology Department, The Hillingdon Hospitals NHS Foundation Trust, London, United Kingdom
9Haematology, University Hospitals Dorset NHS Foundation Trust, Dorset, United Kingdom
10Haematology Department, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, United Kingdom
11Haematology Department, York and Scarborough Teaching Hospitals NHS Foundation Trust, York, United Kingdom
12Haematology Department, University Hospitals Dorset NHS Foundation Trust, Dorset, United Kingdom
13Haematological Malignancy Diagnostic Service, Leeds Teaching Hospital NHS Trust, Leeds, England, United Kingdom
14Nottingham University Hospital, Nottingham, United Kingdom
15Haematology, Dartford and Gravesham NHS Trust, Dartford, United Kingdom
16Department of Clinical Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
17Haematology Department, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
18Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom
19Haematology Department, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
20Department of Haematology, University College London Hospital, London, United Kingdom
21Department of Haematology, University College Hospital, University College of London Hospitals NHS Foundation Trust, London, United Kingdom
22Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, United Kingdom
23Department of Haematology, University College London Hospitals NHS Trust, London, ENG, United Kingdom
24Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
25Haematology Department, Newcastle Hospitals NHS Foundation Trust, Newcastle, United Kingdom
26The Christie NHS Foundation Trust, Manchester, United Kingdom
27Guy's and St Thomas' NHS Foundation Trust, London, ENG, United Kingdom
28Medical Research Council (MRC) Weatherall Institute of Molecular Medicine (WIMM), University of Oxford, Oxford, ENG, United Kingdom
29Oxford University Hospitals NHS Trust, Oxford, United Kingdom

Introduction

Momelotinib (GS-0387) is a small-molecule inhibitor targeting Janus kinase 1 and 2 (JAK1/2) and activin receptor-like kinase 2 (ALK2), developed for myelofibrosis (MF). It inhibits JAK1/2-mediated cytokine signalling and ACVR1-mediated hepcidin production, addressing both myeloproliferative and anemia components of MF. In the UK, Momelotinib was available via a compassionate-access programme from 2023 and approved January 2024 for MF patients with moderate or severe anemia. This study investigates momelotinib's real-world efficacy and safety across the UK.

Methods

Data were collected retrospectively from 16 UK centers. All patients who received momelotinib for MF outside of a clinical trial setting were included. Data on MPN characteristics, transfusion requirements, total symptom scores (TSS), blood tests, and spleen measurements were collected at baseline, 6 weeks, and 3 months post-treatment initiation via clinical examination, US or CT measurement. Anemia and clinical responses were evaluated per ELN response criteria for MF.

Results

The study included 85 patients with MF (62% male, 38% female), median age 72.1 years (IQR: 65.8-76.3 years). Diagnoses were primary MF (52.9%), post-polycythemia vera MF (15.3%), and post-essential thrombocythemia MF (30.6%). Molecular profiling revealed JAK2 V617F (64.7%), CALR (18.8%), MPL (12.9%), and “triple-negative” (5.9%). Most patients (77.6%) had previously received a JAK inhibitor (JAKi), while 22.4% were JAKi naive. Secondary mutations included ASXL1 (30.6%), DNMT3A (10.6%), and TET2 (10.6%). DIPSS+/DIPSS scores were available in 76/85 patients with most being Intermediate-2 or high (77.6%).

Efficacy outcomes in 21 patients who had paired measurements showed that 43% achieved a reduction in spleen size as per ELN response criteria. TSS where paired data were available in 21 patients, improved significantly in 24% of patients, defined as ≥50% symptom score reduction at 3 months. Anemia responses, defined as a ≥20 g/L increase in haemoglobin (Hb) or becoming transfusion independent, were available in 79/85 patients. 36.7% and 43.8% of cases achieved an anaemia response at 6 weeks and 3 months, respectively. Haemoglobin concentration increased significantly at 6 weeks (p<10-4) and 3 months (p<10-4) compared to baseline (matched-pairs Wilcoxon signed-rank test) with a mean increase of 10.8 and 9.2 g/L respectively.

The safety profile was consistent with clinical trial data. 75% of patients continued treatment without significant adverse events after a median follow up of 7.6 months. Discontinuation was due to toxicity (12%), refractory/progressive disease (6%), and HSCT (2.4%). Median overall survival (OS) (censored at HSCT) was not reached (NR), with a 12-month survival rate of 82.5% (95% CI: 67.2%-91.1%). Median event-free survival (EFS) was NR (95% CI: 15.6 months-NE), 6-month EFS 82% (95% CI 70.8-89.2%) (events defined as first occurrence of: permanent discontinuation due to toxicity, disease refractoriness/progression, blast-phase evolution, or death). Grade 3 side effects were reported in 9/85 patients, including thrombocytopenia, fatigue, raised ALT, hyperkalemia, vision loss (cause under investigation), dermatosis, and chest infection. Eleven patients died, 10/11 from AML or progressive disease, and one from a subdural hematoma in the presence of severe thrombocytopenia.

Conclusion

Momelotinib demonstrated significant efficacy in reducing spleen volume, improving anemia, and alleviating symptoms in a substantial proportion of MF patients, including as both a 1st or 2nd line JAKi, with a reasonable safety profile. These real-world results support its use as a viable treatment option for myelofibrosis in routine clinical practice.

Disclosures: Wadelin: GSK: Membership on an entity's Board of Directors or advisory committees; Novartis: Speakers Bureau; BMS: Speakers Bureau. Godfrey: Celgene/BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; AOP: Membership on an entity's Board of Directors or advisory committees. Lambert: Blueprint: Consultancy; Novartis: Honoraria; Takeda: Honoraria; Kite-Gilead: Consultancy, Honoraria. Mead: Karyopharm: Consultancy, Honoraria; GSK: Consultancy, Honoraria, Research Funding; Alethiomics: Consultancy, Current equity holder in private company, Current holder of stock options in a privately-held company, Research Funding; Incyte: Consultancy, Honoraria; Galecto: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Medscape: Honoraria; Ionis: Consultancy, Honoraria; Morphosys: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Roche: Research Funding. McLornan: Imago Biosciences: Research Funding; Abbvie: Honoraria; Jazz Pharma: Honoraria; Novartis: Honoraria. Innes: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Conference fees, Speakers Bureau; Incyte: Speakers Bureau. McGregor: Novartis: Other: Conferences fees, Advisory board, Speakers Bureau; GSK: Speakers Bureau. Somervaille: CellCentric Ltd: Research Funding; Novartis: Consultancy; BMS: Consultancy; GSK: Consultancy; MSD: Consultancy. Harrison: Sobi: Consultancy; Keros: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy; Geron: Consultancy; Galecto: Consultancy; IMAGO: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau; AOP: Consultancy, Honoraria, Speakers Bureau; CTI: Ended employment in the past 24 months; Incyte: Consultancy, Honoraria, Other: Teaching and Speaking; Research: PI, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: Teaching and speaking; Research: PI, Speakers Bureau; MorphoSys/Constellation: Consultancy, Honoraria, Other: Research: PI, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Other: Teaching and speaking; Research: PI, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Teaching and speaking; Research: PI, Research Funding, Speakers Bureau; MPN voice: Other: Leadership role. Harrington: Incyte: Honoraria, Research Funding; GSK: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Constellation: Research Funding; AOP: Research Funding. Psaila: University of Oxford: Patents & Royalties: 2203947.3; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy; Incyte: Consultancy, Research Funding; Alethiomics: Consultancy, Current equity holder in private company, Research Funding.

*signifies non-member of ASH